Association of Matrix Metalloproteinase 7 Expression With Pathologic Response After Neoadjuvant Treatment in Patients With Resected Pancreatic Ductal Adenocarcinoma
Authors: Sami Shoucair, Jianan Chen, James R. Martinson, Joseph R. Habib, Benedict Kinny-Köster, Ning Pu, A. Floortje van Oosten, Ammar A. Javed, Eun Ji Shin, Syed Z. Ali, Kelly J. Lafaro, Christopher L. Wolfgang, Jin He, Jun Yu
Journal: JAMA Surgery (2022)

<h3>Importance</h3> The use of neoadjuvant therapy (NAT) in resectable pancreatic ductal adenocarcinoma (PDAC) remains controversial. A favorable pathologic response (complete or marked tumor regression) to NAT is associated with better outcomes in patients with resected PDAC. The role of NAT for early systemic control compared with immediate surgical resection for PDAC is under investigation. In the era of precision medicine, biomarkers for patient selection and prediction of therapy response are crucial. <h3>Objective</h3> To evaluate the use of assessment for protein expression on fine-needle aspiration (FNA) biopsy specimens in predicting pathologic response to NAT in treatment-naive patients. <h3>Design, Setting, and Participants</h3> This was a single-institution prognostic study from a high-volume center for pancreatic cancer. All specimens were obtained between January 1, 2009, and December 31, 2018, with a median (SE) follow-up of 20.2 (1.4) months. Analysis of the data was performed from October 1, 2019, to April 30, 2021. Targeted RNA sequencing of frozen FNA biopsy specimens from a discovery cohort of 23 patients was performed to identify genes with aberrant expression that was associated with patients' pathologic response to NAT. Immunohistochemical staining was performed on an additional 80 FNA biopsy specimens to assess expression of matrix metalloproteinase 7 (MMP-7) and its association with pathologic response. Receiver operating characteristic curves for prediction of favorable pathologic response were determined. <h3>Results</h3> In the discovery cohort (12 [52.1%] male; 3 [13.0%] Black and 20 [86.9%] White), RNA sequencing showed that lower MMP-7 expression was associated with favorable pathologic response (College of American Pathologists system scores of 0 [complete response] and 1 [marked response]). In the validation cohort (40 [50.0%] female; 9 [11.3%] Black and 71 [88.7%] White), patients with negative MMP-7 expression were significantly more likely to have a favorable pathologic response (odds ratio, 21.25; 95% CI, 6.19-72.95;<i>P</i> = .001). Receiver operating characteristic curves for prediction of favorable pathologic response from multivariable Cox proportional hazards regression modeling showed that MMP-7 expression increased the area under the curve from 0.726 to 0.906 (<i>P</i> &lt; .001) even after stratifying by resectability status. The positive predictive value and negative predictive value of MMP-7 protein expression on FNA biopsy specimens in predicting unfavorable pathologic response (scores of 2 [partial response] or 3 [poor or no response]) were 88.2% and 73.9%, respectively. <h3>Conclusions and Relevance</h3> Assessment of MMP-7 expression on FNA biopsy specimens at the time of diagnosis may help identify patients who would benefit the most from NAT.